Several publications and patent documents are cited throughout the specification in order to describe the state of the art to which this invention pertains. Each of these citations is incorporated herein by reference as though set forth in full.
Cancer cells and normal cells are metabolically different. Ninety years ago Otto Warburg found that while normal adult cells rely on mitochondrial oxidative phosphorylation to generate energy, cancer cells revert to a more primitive method of metabolizing glucose, aerobic glycolysis, fermenting glucose into lactate even in the presence of enough oxygen to support oxidative phosphorylation. Warburg proposed that this phenomenon (now called the Warburg effect) is an early step on the road to tumorigenesis. The Warburg effect has been demonstrated to occur across a wide spectrum of tumors and is found in about 70% of cases. It is generally accepted as a metabolic hallmark of cancer and is exploited by clinicians for the detection of tumors by 18-fluorodeoxyglucose positron emission tomography.
Lung tumors are already treated locally to achieve local control. 125I seed implantation along the resected margin for patients undergoing limited resection of lung cancer results in a relatively low incidence of local recurrence and may prolong survival (Lee et al. (2003) The Annals of Thoracic Surgery 75:237).
Aerosol formulations of anti-diabetic agents have been proposed to treat diabetes or a diabetes related condition susceptible of treatment by inhalation (U.S. Pat. No. 6,645,468). However, many drugs that are administered orally can be toxic to the lung when inhaled (Wolff et al. (1993) Crit. Rev. Toxicol., 23:343-369).